1. Field of the Invention
The invention is drawn to methods for the treatment of drug abuse, particularly cocaine and dual cocaine and opiate, abuse and dependence.
2. Brief Description of the Background Art
Cocaine abuse has reached epidemic proportions in the general population (Kozel, N. J., et al.. Science 234:970 (1986); National Institute on Drug Abuse. ADAMHA, Request for Application DA-89-01 (1988)) and has also increased among heroin-dependent persons, including those in methadone maintenance treatment programs (Kosten, T. R., et al., Am. J. Drug Alcohol Abuse 12:1 (1986); Kaul, B., et al., ibid. 8:27 (1981)). The many adverse medical consequences of cocaine abuse (Cregler, L. L., et al., N. Engl. J. Med. 315:1495 (1986); Mendelson, J. H., et al., Harrison's Principles of Internal Medicine. McGraw-Hill, New York (1986)) are further augmented by the combined use of cocaine and heroin (Kreek, M. J., Psychopharmacology: The Third Generation of Progress. Raven, New York (1987)). Dual addiction to intravenous cocaine and heroin use is likely to increase risk for AIDS, both through needle sharing and through the combined immuno-suppressive effects of both drugs (Donahoe, R. M., et al., Psychological, Neuropsychiatric and Substance Abuse Aspects of AIDS. Raven, New York (1988); Klein, T. W., et al. ibid (1988)). Intravenous drug abuse was estimated to account for over 30% of AIDS victims in the United States in 1988 (Kozel, N. J., et al., Science 234:970 (1986); National Institute on Drug Abuse. ADAMHA, Request for Applications DA-89-01 (1988)).
At present, there is no uniformly effective pharmacotherapy for cocaine abuse (Kleber, H. D., et al. J Clin. Psychiatry 45:18 (1984); Gawin, F. H., et al., N. Eng. J. Med. 318:1173 (1988)), and the dual abuse of cocaine plus heroin is an even more difficult treatment challenge. Heroin abuse can be treated with opiate agonists (methadone and 1-alpha-acetylmethadol [LAAM]) (Dole, V. P., et al., J. Am. Med. Assoc. 193:646 (1965); Blaine, J. B., et al., Recent Developments in Chemotherapy of Narcotic Addiction. Ann. New York. Acad. Sci. 311:214 (1978); Blaine, J. B., et al., Research Developments in Drug and Alcohol Use. Ann. New York. Acad. Sci. 362:101 (1981)) and the opiate antagonist naltrexone (Meyer, R. E., et al., The Heroin Stimulus, Plenum, New York (1979); Martin, W. R., et al., Arch. Gen. Psychiatry 28:784 (1973); Mello, N. K., et al., J. Pharmocol. Exp. Ther. 216:45 (1981)), but these pharmacotherapies have not proved useful for combined cocaine and heroin abuse (Kosten, T. R., et al., Arch. Gen. Psychiatry 44:281 (1987)). Although desipramine (a tricyclic antidepressant) reduces cocaine abuse in some patients (Kleber, H. D., et al. J. Clin. Psychiatry 45:18 (1984); Gawin, F. H., et al., N. Eng. J. Med. 318:1173 (1988); Gawin, F. H., et al., Arch. Gen. Psychiatry 41:903 (1984); Tennant, F. S., et al., Problems of Drug Dependence, 1982, Committee on Problems of Drug Dependence, Washington, D.C. (1983)), it may stimulate relapse to cocaine abuse in abstinent patients (Weiss, R. E., J. Am. Med. Assoc. 260:2545 (1988)). Treatment with methadone and desipramine has yielded inconsistent results on cocaine use by heroin abusers (O'Brien, C. P., et al., J. Clin. Psychiatry 49:17 (1988); Kosten, T. R., et al., ibid 48:442 (1987)).
The present invention provides methods utilizing pharmacotherapies which antagonize the reinforcing effects of cocaine and has minimal adverse side effects or potential for abuse liability.